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Role of stress echocardiography in heart failure
Role of Stress Echocardiography in Heart Failure Luc A. Pierard,
MD,
and Etienne P. Hoffer,
MD
Most patients presenting with heart failure have severe coronary artery disease. The identification of viable hibernating myocardium is of paramount clinical importance for a correct indication of revascularization. Contractile reserve may be identified when regional asynergy improves during low or moderate doses of dobutamine. Dipyridamole, given at infra-low dose, alone or preferably in association with a low dose of dobutamine, is another possible pharmacologic stress protocol. Dobutamine echocardiography has been found to be more specific than thallium scintigraphy for predicting functional recovery after revascularization. However, the absence of contractile reserve does not
exclude the presence of myocardial viability: perfusion reserve may be too low because of a critical coronary artery stenosis, or profound ultrastructural changes of myocardial cells may be present, including significant loss of contractile material. Inotropic reserve can also be assessed by dobutamine stress echocardiography in patients with idiopathic cardiomyopathy. The evolution of hemodynamic variables can be measured during the stress test. Stress echocardiography, especially during exercise, could probably provide important information about heart failure associated with valvular heart disease. Q1998 by Excerpta Medica, Inc. Am J Cardiol 1998;81(12A):111G–114G
n patients with coronary artery disease and chronic left ventricular dysfunction, it is crucial to distinIguish between viable and fibrotic tissue to make ade-
toms at rest. When coronary flow is restored, recovery of contractile function can take several days, weeks, or even months. Since no long-term experimental model exists, the physiopathology of myocardial hibernation remains unclear. It is known to be associated with marked ultrastructural alterations in the myocytes, including loss of myofilaments and contractile material.7 Several techniques can be used for identification of hibernating myocardium: pharmacologic stress echocardiography identifies contractile reserve, positron emission tomography allows the measurement of flow and metabolic activity, and thallium-201 single-photon emission computed tomography (SPECT, or scintigraphy) assesses perfusion and membrane integrity. More recently, contrast echocardiography and nuclear magnetic resonance imaging have demonstrated their usefulness for the assessment of myocardial viability.
quate clinical decisions. Patients with evidence of hibernating myocardium who do not undergo revascularization have a poor prognosis with a high incidence of cardiac events. In contrast, evidence of viable myocardium in patients undergoing successful revascularization is associated with longer survival1 and improvement of both symptoms2 and ventricular function.3 Several years ago, low-dose dobutamine echocardiography was introduced as a method for detecting contractile reserve in the setting of acute myocardial infarction.4 Further studies have extended these observations to patients with chronic ischemic heart disease. The detection of myocardial viability by means of echocardiography is clinically attractive because ultrasound imaging is widely available, noninvasive, and can be performed at low cost.
MYOCARDIAL VIABILITY Noncontractile but viable myocardium may correspond to different myocardial states that are important but difficult to distinguish, i.e., ischemia, stunning, nontransmural infarction, or hibernation.5 In individual patients, these myocardial states may coexist. The term “hibernating myocardium” was first introduced by Rahimtoola6 to describe left ventricular dysfunction resulting from chronic myocardial ischemia and demonstrating recovery of function after myocardial revascularization. In this phenomenon, the downregulation of myocardial contractile function represents an adaptation of myocytes to balance oxygen demand and supply, by decreasing oxygen consumption, thus preventing myocardial necrosis and ischemic sympFrom the Department of Cardiology, University Hospital, Lie`ge, Belgium. Address for reprints: L. Pierard, MD, CHU Sart Tilman Cardiology, B-4000 Lie`ge, Belgium. ©1998 by Excerpta Medica, Inc. All rights reserved.
PHARMACOLOGIC STRESS ECHOCARDIOGRAPHY AND CONTRACTILE RESERVE Absence of wall thickening at rest does not necessarily imply myocardial necrosis. Dysfunctional but viable myocardium must be distinguished from myocardial necrosis, because mechanical function can recover either spontaneously (if the myocardium is stunned) or after a revascularization procedure (if it is hibernating). The detection of contractile reserve and the distinction between stunning and hibernation are of importance in patients with coronary artery disease and chronic ventricular dysfunction. Dobutamine stress echocardiography has emerged as a new noninvasive clinical tool available for the detection of both stunned and hibernating myocardium. Viable myocardium retaining contractile reserve will demonstrate improved regional thickening during dobutamine administration. The major studies published during the last few years concerning the role of pharmacologic stress echocardiography for the detection of myocardial con0002-9149/98/$19.00 PII S0002-9149(98)00066-6
111G
TABLE I Sensitivity and Specificity of Pharmacologic Stress Echocardiography for the Detection of Myocardial Contractile Reserve in Patients Undergoing Revascularization Authors Cigarroa8 Afridi9 La Canna10 Perrone-Filardi11 Meluzin12 Elhendy13 Picano14 Picano15 Marzullo17 Charney18 Arnese19 Vanoverschelde20
Pharmacologic Agent
Patients n
Sensitivity (%)
Specificity (%)
Dobutamine Dobutamine Dobutamine Dobutamine Dobutamine Dobutamine Dipyridamole Dobutamine 1 dipyridamole Dobutamine Dobutamine Dobutamine Dobutamine
49 20 33 18 37 42 34 34 14 17 38 73
NA NA 87 88 NA 58 67 94 82 71 74 75
NA NA 82 87 NA 94 95 89 92 93 95 86
tractile reserve and prediction of recovery after revascularization are summarized in Table I. In the study by Cigarroa et al,8 dobutamine stress echocardiography (5–20 mg/kg per min) was performed in 49 consecutive patients with multivessel coronary artery disease and depressed left ventricular function (ejection fraction ,45%). Contractile reserve was present in 24 patients; 25 patients underwent successful revascularization. Results showed that 9 of 11 patients who demonstrated improved systolic wall thickening after bypass grafting had contractile reserve during dobutamine stress echocardiography (sensitivity 82%), whereas 12 of 14 patients without contractile reserve did not improve (specificity 86%). Afridi et al9 studied 20 patients with stable coronary artery disease scheduled for coronary angioplasty. Dobutamine testing was performed using incremental doses of 2.5– 40 mg/kg per min. The administration of low and high doses was important, since the predictive value for functional recovery was higher in the presence of a biphasic response (improvement at low dose and worsening at high dose: 72%) than in presence of sustained improvement throughout the test (15%) or no change response (13%). La Canna et al10 studied 33 patients (23 with angina and 10 with dyspnea) who were scheduled for coronary artery bypass grafting. Dobutamine stress echocardiography (5–10 mg/kg per min) predicted functional recovery with a sensitivity of 87% and a specificity of 82%. Using the same low-dose dobutamine test, Perrone-Filardi et al11 also confirmed this good predictive value but found a better sensitivity for identifying reversible dysfunctional myocardium in hypokinetic segments rather than akinetic segments (88% vs 69%). Meluzin et al12 found a high correlation between the number of segments with contractile reserve and the improvement in left ventricular ejection fraction after angioplasty or coronary bypass grafting. In a recent study including 42 patients with coronary artery disease and left ventricular dysfunction, undergoing coronary artery bypass surgery, Elhendy et al13 found that akinetic segments becoming dyskinetic during high-dose dobutamine were associated with the absence of contractile reserve during low112G THE AMERICAN JOURNAL OF CARDIOLOGYT
dose dobutamine and poor functional outcome after surgical revascularization. In a heterogeneous population of patients with recent and old infarctions, Picano et al14 demonstrated that dipyridamole echocardiography (up to 0.84 mg/kg over 10 minutes) can identify regions with myocardial viability. More recently, this group15 also demonstrated that combined low-dose dipyridamole (0.28 mg/kg during 4 minutes) and low-dose dobutamine (5 and 10 mg/kg per min, each dose during 5 minutes) could recruit a contractile reserve in some asynergic segments that were nonresponders after dobutamine or dipyridamole alone. The prognostic value of dobutamine stress echocardiography was recently studied in 108 medically treated patients with poor left ventricular function.16 The investigators found that the event rate after a 16 6 8 months follow-up was significally higher in patients with viable or ischemic myocardium than in those with scar (43% vs 8%).
COMPARISON WITH OTHER TECHNIQUES Several studies have compared the predictive value of dobutamine echocardiography and thallium scintigraphy for the detection of myocardial viability. Marzullo et al17 compared the utility of resting planar thallium-201 scintigraphy, technetium-99m sestamibi scintigraphy, and dobutamine stress echocardiography in detecting myocardial viability in 14 patients with previous myocardial infarction. Dobutamine stress echocardiography, thallium-201 scintigraphy, and sestamibi scintigraphy correctly identified 82%, 86%, and 75% of postoperative viable segments and 92%, 92%, and 84% of postoperative nonviable segments, respectively. Sestamibi tended to underestimate the incidence of viability. Charney et al18 found similar concordant results in 17 patients. They found a better positive predictive value using 10 mg/kg per min of dobutamine rather than 5 mg/kg per min (92% vs 78%) but a lower negative predictive value with the infusion of 10 mg/kg per min (74% vs 86%). In contrast, Arnese et al19 studied 38 patients with severe left ventricular dysfunction (ejection fraction ,40%)
VOL. 81 (12A)
JUNE 18, 1998
and found that thallium-201 scintigraphy overestimated the probability of postrevascularization improvement of dyssynergic segments. Comparing these two techniques in a population of 73 and 30 patients undergoing revascularization, Vanoverschelde et al20 and Panza et al21 found similar results. These investigators suggest that the cellular mechanisms responsible for a positive inotropic response to adrenergic stimulation require a higher degree of myocyte functional integrity than those responsible for thallium uptake. Therefore, the absence of contractile reserve with dobutamine does not exclude any residual myocardial viability. Comparing dobutamine transesophageal echocardiography (5–20 mg/kg per min) with [18F]fluorodeoxyglucose positron emission tomography— generally considered as “the gold standard” technique,— Baer et al22 found very concordant results for the detection of myocardial viability in akinetic segments.
PROTOCOL AND INTERPRETATION No serious complications have been described during pharmacologic stress testing in patients with poor left ventricular function. Ventricular, or more often supraventricular, arrhythmias can be induced during the perfusion of inotropic agents. Because of the very short elimination half-time of these agents, the arrhythmias disappeared very quickly after stopping the infusion. Contractile reserve is defined as an improvement in wall thickening during perfusion of inotropic or vasodilator agents. This involves a certain degree of subjective interpretation. Measurement of wall thickening using M-mode may help to quantify this improvement, but this is only possible in limited areas. In patients with severe coronary artery disease, the administration of inotropic or vasodilator agents, even in a relatively low dose, can sometimes precipitate myocardial ischemia when a severe coronary stenosis is present. It is therefore recommended to start the pharmacologic test with a very low dose (such as 2.5 mg/kg per min of dobutamine) and to use 3–5-minute steps with continuous echocardiographic recording. The dose of dobutamine required to elicit contractile reserve is dependent on infarct size. In the presence of a large infarction, 20 mg/kg per min or even more are sometimes necessary to induce the improvement in myocardial contractility. In the presence of a significant stenosis in the infarct-related vessel, a biphasic response may be observed: an initial improvement in wall thickening during low-dose dobutamine is followed by a worsening of contractility at higher doses when the ischemic threshold is reached. Beta blockers should be stopped at least 24 –36 hours before the test. In patients with severe coronary artery stenosis who present tachycardia at baseline, the ischemic threshold may be attained before the administration of the inotropic agent.
FURTHER PERSPECTIVES Echocardiography provides the opportunity to noninvasively explore hemodynamic variables during pharmacologic or exercise stress test. It could also be useful in heart failure associated with valvular disease. The management of patients with critical aortic stenosis and severe left ventricular dysfunction is sometimes extremely difficult. The selection of patients who may benefit from valve replacement can be improved by the measurement of transvalvular gradients and cardiac output during dobutamine administration. The incidence of dynamic mitral regurgitation is underestimated in patients with coronary artery disease. Dynamic mitral regurgitation is ideally evaluated by an exercise stress test, alone or in combination with right heart catheterization. Further studies are needed in this field. Contrast echocardiography has also been found to be a valuable method for detecting myocardial viability. Some investigators suggest that this technique is as accurate as dobutamine echocardiography.23 This technique also provides important information on the presence of microvascular integrity.
CONCLUSIONS Pharmacologic stress echocardiography is a safe and accurate tool for the assessment of contractile reserve. In experienced hands, this method provides clinically relevant information about patients with severe left ventricular dysfunction. Several studies have demonstrated its value in predicting improvement of left ventricular function in patients undergoing revascularization. Other applications need to be studied such as the assessement of valvular dysfunction or hemodynamic parameters during an exercise protocol. 1. Nesto RW, Cohn LH, Wynne J, Holman L, Cohn PF. Inotropic contractile reserve: a useful predictor of increased 5 year survival and improved postoperative left ventricular function in patients with coronary artery disease and reduced ejection fraction. Am J Cardiol 1982;50:39 – 44. 2. Schelbert HR. Merits and limitations of radionuclide approaches to viability and future developments. J Nucl Cardiol 1994;1:86 – 89. 3. Marwick T, MacIntyre W, Lafont A, Nemec J, Salcedo E. Metabolic responses of hibernating and infarcted myocardium to revascularization: a follow-up study of regional perfusion, function and metabolism. Circulation 1992;8:1347–1353. 4. Pie´rard LA, De Landsheere C, Berthe C, Rigo P, Kulbertus H. Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction treated by thrombolysis: a comparison with positron emission tomography. J Am Coll Cardiol 1990;15:1921–1031. 5. Schutz R, Heusch G. Characterization of hibernating and stunned myocardium. Eur Heart J 1995;16(suppl J):19 –25. 6. Rahimtoola SH. The hibernating myocardium. Am Heart J 1989;117:211–213. 7. Flameng W, Suy R, Schwarz F,Borgers M, Piessens J, Thone F, Van Ermen H, De Geest H. Ultrastructural correlates of left ventricular contraction abnormalities in patients with chronic ischemic heart disease: determinants of reversible segmental asynergy post-revascularization surgery. Am Heart J 1981;102:846 – 857. 8. Cigarroa CG, De Filippi CR, Brickner ME, Alvarez LG, Wait MA, Grayburn PA. Dobutamine stress echocardiography identifies hibernating myocardium and predicts recovery of left ventricular function after coronary revascularization. Circulation 1993;88:430 – 436. 9. Afridi I, Keiman NS, Raizner AE, Zoghbi WA. Dobutamine echocardiography in myocardial hibernation: optimal dose and accuracy in predicting recovery of ventricular function after coronary angioplasty. Circulation 1995;91:663– 670. 10. La Canna G, Alfieri O, Giubbibi R, Gargano M, Ferrari R, Visioli O. Echocardiography during infusion of dobutamine for identification of reversible dysfunction in patients with chronic coronary artery disease. J Am Coll Cardiol 1994;23:617– 626. 11. Perrone-Filardi P, Pace L, Prastaro M, Piscione F, Betocchi S, Squame F, Vezzuto P, Soricelli A, Indolfi C, Salvatore M, Chiariello M. Dobutamine echocardiography predicts improvement of hypoperfused dysfunctional myocar-
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dium after revascularization in patients with coronary artery disease. Circulation 1995;91:2556 –2565. 12. Meluzin J, Cigarroa CG, Brickner ME, Cerny J, Spinarova L, Frelich M, Stetka F, Groch L, Grayburn PA. Dobutamine echocardiography in predicting improvement in global left ventricular systolic function after coronary bypass or angioplasty in patients with healed myocardial infarcts. Am J Cardiol 1995;76: 877– 880. 13. Elhendy A, Cornel JH, Roelandt JRTC, van Domburg RT, Fioretti PM. Akinesis becoming dyskinesis during dobutamine stress echocardiography: a predictor of poor functional recovery after surgical revascularization. Chest 1996;110:155–158. 14. Picano E, Marzullo P, Gigli G, Reisenhofer B, Parodi O, Distante A, L’Abbate A. Identification of viable myocardium by dipyridamole-induced improvement in regional left ventricular function assessed by echocardiography in myocardial infarction and comparison with thallium scintigraphy at rest. Am J Cardiol 1992;70:703–710. 15. Picano E, Ostojic M, Varga A, Sicari R, Djordjevic-Dikic A, Nedelikovic I, Torres M. Combined low dose dipyridamole-dobutamine stress echocardiography to identify myocardial viability. J Am Coll Cardiol 1996;27:1422–1428. 16. Williams MJ, Odabashian J, Lauer MS, Thomas JD, Marwick TH. Prognostic value of dobutamine echocardiography in patients with left ventricular dysfunction. J Am Coll Cardiol 1996;27:132–139. 17. Marzullo P, Parodi O, Reisenhofer B, Sambuceti G, Picano E, Distante A, Gimelli A, L’Abbate A. Value of rest thallium-201/technetium-99m sestamibi scans and dobutamine echocardiography for detecting myocardial viability. Am J Cardiol 1993;71:166 –172. 18. Charney R, Schwinger ME, Chun J, Cohen MV, Nanna M, Menegus MA,
114G THE AMERICAN JOURNAL OF CARDIOLOGYT
Wexler J, Spindola Franco H, Greenberg MA. Dobutamine echocardiography and resting-redistribution thallium-201 scintigraphy predicts recovery of hibernating myocardium after coronary revascularization. Am Heart J 1994;128:864 – 869. 19. Arnese M, Cornel JH, Salustri A, Maat APWM, Elhendy A, Reijs AEM, Ten Cate FJ, Keane D, Balk AHMM, Roelandt JRTC, Fioretti PM. Prediction of improvement of regional left ventricular function after surgical revascularization: a comparison of low-dose dobutamine echocardiography with 201Tl singlephoton emission computed tomography. Circulation 1995;91:2748 –2752. 20. Vanoverschelde JLJ, D’Hondt AM, Marwick T, Gerber BL, De Kock M, Dion R, Wijns W, Melin JA. Head-to-head comparison of exercise-redistributionreinjection thallium single-photon emission computed tomography and low dose dobutamine echocardiography for prediction of reversibility of chronic left ventricular ischemic dysfunction. J Am Coll Cardiol 1996;28:432– 442. 21. Panza J, Disizian V, Laurienzo J, Curiel R, Katsiyiannia P. Relation between thallium uptake and contractile response to dobutamine: implications regarding myocardial viability in patients with chronic coronary artery disease and left ventricular dysfunction. Circulation 1995;91:990 –998. 22. Baer FM, Voth E, Deutsch HJ, Schneider CA, Schicha H, Sechtem U. Assessment of viable myocardium by dobutamine transesophageal echocardiography and comparison with fluorine-18 fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 1994;24:343–353. 23. DeFilippi C, Willett D, Irani W, Eichhorn E, Velasco C, Grayburn P. Comparison of myocardial contrast echocardiography and low-dose dobutamine stress echocardiography in predicting recovery of left ventricular function after coronary revascularization in chronic ischemic heart disease. Circulation 1995; 92:2863–2868.
VOL. 81 (12A)
JUNE 18, 1998
MD,
and Etienne P. Hoffer,
MD
Most patients presenting with heart failure have severe coronary artery disease. The identification of viable hibernating myocardium is of paramount clinical importance for a correct indication of revascularization. Contractile reserve may be identified when regional asynergy improves during low or moderate doses of dobutamine. Dipyridamole, given at infra-low dose, alone or preferably in association with a low dose of dobutamine, is another possible pharmacologic stress protocol. Dobutamine echocardiography has been found to be more specific than thallium scintigraphy for predicting functional recovery after revascularization. However, the absence of contractile reserve does not
exclude the presence of myocardial viability: perfusion reserve may be too low because of a critical coronary artery stenosis, or profound ultrastructural changes of myocardial cells may be present, including significant loss of contractile material. Inotropic reserve can also be assessed by dobutamine stress echocardiography in patients with idiopathic cardiomyopathy. The evolution of hemodynamic variables can be measured during the stress test. Stress echocardiography, especially during exercise, could probably provide important information about heart failure associated with valvular heart disease. Q1998 by Excerpta Medica, Inc. Am J Cardiol 1998;81(12A):111G–114G
n patients with coronary artery disease and chronic left ventricular dysfunction, it is crucial to distinIguish between viable and fibrotic tissue to make ade-
toms at rest. When coronary flow is restored, recovery of contractile function can take several days, weeks, or even months. Since no long-term experimental model exists, the physiopathology of myocardial hibernation remains unclear. It is known to be associated with marked ultrastructural alterations in the myocytes, including loss of myofilaments and contractile material.7 Several techniques can be used for identification of hibernating myocardium: pharmacologic stress echocardiography identifies contractile reserve, positron emission tomography allows the measurement of flow and metabolic activity, and thallium-201 single-photon emission computed tomography (SPECT, or scintigraphy) assesses perfusion and membrane integrity. More recently, contrast echocardiography and nuclear magnetic resonance imaging have demonstrated their usefulness for the assessment of myocardial viability.
quate clinical decisions. Patients with evidence of hibernating myocardium who do not undergo revascularization have a poor prognosis with a high incidence of cardiac events. In contrast, evidence of viable myocardium in patients undergoing successful revascularization is associated with longer survival1 and improvement of both symptoms2 and ventricular function.3 Several years ago, low-dose dobutamine echocardiography was introduced as a method for detecting contractile reserve in the setting of acute myocardial infarction.4 Further studies have extended these observations to patients with chronic ischemic heart disease. The detection of myocardial viability by means of echocardiography is clinically attractive because ultrasound imaging is widely available, noninvasive, and can be performed at low cost.
MYOCARDIAL VIABILITY Noncontractile but viable myocardium may correspond to different myocardial states that are important but difficult to distinguish, i.e., ischemia, stunning, nontransmural infarction, or hibernation.5 In individual patients, these myocardial states may coexist. The term “hibernating myocardium” was first introduced by Rahimtoola6 to describe left ventricular dysfunction resulting from chronic myocardial ischemia and demonstrating recovery of function after myocardial revascularization. In this phenomenon, the downregulation of myocardial contractile function represents an adaptation of myocytes to balance oxygen demand and supply, by decreasing oxygen consumption, thus preventing myocardial necrosis and ischemic sympFrom the Department of Cardiology, University Hospital, Lie`ge, Belgium. Address for reprints: L. Pierard, MD, CHU Sart Tilman Cardiology, B-4000 Lie`ge, Belgium. ©1998 by Excerpta Medica, Inc. All rights reserved.
PHARMACOLOGIC STRESS ECHOCARDIOGRAPHY AND CONTRACTILE RESERVE Absence of wall thickening at rest does not necessarily imply myocardial necrosis. Dysfunctional but viable myocardium must be distinguished from myocardial necrosis, because mechanical function can recover either spontaneously (if the myocardium is stunned) or after a revascularization procedure (if it is hibernating). The detection of contractile reserve and the distinction between stunning and hibernation are of importance in patients with coronary artery disease and chronic ventricular dysfunction. Dobutamine stress echocardiography has emerged as a new noninvasive clinical tool available for the detection of both stunned and hibernating myocardium. Viable myocardium retaining contractile reserve will demonstrate improved regional thickening during dobutamine administration. The major studies published during the last few years concerning the role of pharmacologic stress echocardiography for the detection of myocardial con0002-9149/98/$19.00 PII S0002-9149(98)00066-6
111G
TABLE I Sensitivity and Specificity of Pharmacologic Stress Echocardiography for the Detection of Myocardial Contractile Reserve in Patients Undergoing Revascularization Authors Cigarroa8 Afridi9 La Canna10 Perrone-Filardi11 Meluzin12 Elhendy13 Picano14 Picano15 Marzullo17 Charney18 Arnese19 Vanoverschelde20
Pharmacologic Agent
Patients n
Sensitivity (%)
Specificity (%)
Dobutamine Dobutamine Dobutamine Dobutamine Dobutamine Dobutamine Dipyridamole Dobutamine 1 dipyridamole Dobutamine Dobutamine Dobutamine Dobutamine
49 20 33 18 37 42 34 34 14 17 38 73
NA NA 87 88 NA 58 67 94 82 71 74 75
NA NA 82 87 NA 94 95 89 92 93 95 86
tractile reserve and prediction of recovery after revascularization are summarized in Table I. In the study by Cigarroa et al,8 dobutamine stress echocardiography (5–20 mg/kg per min) was performed in 49 consecutive patients with multivessel coronary artery disease and depressed left ventricular function (ejection fraction ,45%). Contractile reserve was present in 24 patients; 25 patients underwent successful revascularization. Results showed that 9 of 11 patients who demonstrated improved systolic wall thickening after bypass grafting had contractile reserve during dobutamine stress echocardiography (sensitivity 82%), whereas 12 of 14 patients without contractile reserve did not improve (specificity 86%). Afridi et al9 studied 20 patients with stable coronary artery disease scheduled for coronary angioplasty. Dobutamine testing was performed using incremental doses of 2.5– 40 mg/kg per min. The administration of low and high doses was important, since the predictive value for functional recovery was higher in the presence of a biphasic response (improvement at low dose and worsening at high dose: 72%) than in presence of sustained improvement throughout the test (15%) or no change response (13%). La Canna et al10 studied 33 patients (23 with angina and 10 with dyspnea) who were scheduled for coronary artery bypass grafting. Dobutamine stress echocardiography (5–10 mg/kg per min) predicted functional recovery with a sensitivity of 87% and a specificity of 82%. Using the same low-dose dobutamine test, Perrone-Filardi et al11 also confirmed this good predictive value but found a better sensitivity for identifying reversible dysfunctional myocardium in hypokinetic segments rather than akinetic segments (88% vs 69%). Meluzin et al12 found a high correlation between the number of segments with contractile reserve and the improvement in left ventricular ejection fraction after angioplasty or coronary bypass grafting. In a recent study including 42 patients with coronary artery disease and left ventricular dysfunction, undergoing coronary artery bypass surgery, Elhendy et al13 found that akinetic segments becoming dyskinetic during high-dose dobutamine were associated with the absence of contractile reserve during low112G THE AMERICAN JOURNAL OF CARDIOLOGYT
dose dobutamine and poor functional outcome after surgical revascularization. In a heterogeneous population of patients with recent and old infarctions, Picano et al14 demonstrated that dipyridamole echocardiography (up to 0.84 mg/kg over 10 minutes) can identify regions with myocardial viability. More recently, this group15 also demonstrated that combined low-dose dipyridamole (0.28 mg/kg during 4 minutes) and low-dose dobutamine (5 and 10 mg/kg per min, each dose during 5 minutes) could recruit a contractile reserve in some asynergic segments that were nonresponders after dobutamine or dipyridamole alone. The prognostic value of dobutamine stress echocardiography was recently studied in 108 medically treated patients with poor left ventricular function.16 The investigators found that the event rate after a 16 6 8 months follow-up was significally higher in patients with viable or ischemic myocardium than in those with scar (43% vs 8%).
COMPARISON WITH OTHER TECHNIQUES Several studies have compared the predictive value of dobutamine echocardiography and thallium scintigraphy for the detection of myocardial viability. Marzullo et al17 compared the utility of resting planar thallium-201 scintigraphy, technetium-99m sestamibi scintigraphy, and dobutamine stress echocardiography in detecting myocardial viability in 14 patients with previous myocardial infarction. Dobutamine stress echocardiography, thallium-201 scintigraphy, and sestamibi scintigraphy correctly identified 82%, 86%, and 75% of postoperative viable segments and 92%, 92%, and 84% of postoperative nonviable segments, respectively. Sestamibi tended to underestimate the incidence of viability. Charney et al18 found similar concordant results in 17 patients. They found a better positive predictive value using 10 mg/kg per min of dobutamine rather than 5 mg/kg per min (92% vs 78%) but a lower negative predictive value with the infusion of 10 mg/kg per min (74% vs 86%). In contrast, Arnese et al19 studied 38 patients with severe left ventricular dysfunction (ejection fraction ,40%)
VOL. 81 (12A)
JUNE 18, 1998
and found that thallium-201 scintigraphy overestimated the probability of postrevascularization improvement of dyssynergic segments. Comparing these two techniques in a population of 73 and 30 patients undergoing revascularization, Vanoverschelde et al20 and Panza et al21 found similar results. These investigators suggest that the cellular mechanisms responsible for a positive inotropic response to adrenergic stimulation require a higher degree of myocyte functional integrity than those responsible for thallium uptake. Therefore, the absence of contractile reserve with dobutamine does not exclude any residual myocardial viability. Comparing dobutamine transesophageal echocardiography (5–20 mg/kg per min) with [18F]fluorodeoxyglucose positron emission tomography— generally considered as “the gold standard” technique,— Baer et al22 found very concordant results for the detection of myocardial viability in akinetic segments.
PROTOCOL AND INTERPRETATION No serious complications have been described during pharmacologic stress testing in patients with poor left ventricular function. Ventricular, or more often supraventricular, arrhythmias can be induced during the perfusion of inotropic agents. Because of the very short elimination half-time of these agents, the arrhythmias disappeared very quickly after stopping the infusion. Contractile reserve is defined as an improvement in wall thickening during perfusion of inotropic or vasodilator agents. This involves a certain degree of subjective interpretation. Measurement of wall thickening using M-mode may help to quantify this improvement, but this is only possible in limited areas. In patients with severe coronary artery disease, the administration of inotropic or vasodilator agents, even in a relatively low dose, can sometimes precipitate myocardial ischemia when a severe coronary stenosis is present. It is therefore recommended to start the pharmacologic test with a very low dose (such as 2.5 mg/kg per min of dobutamine) and to use 3–5-minute steps with continuous echocardiographic recording. The dose of dobutamine required to elicit contractile reserve is dependent on infarct size. In the presence of a large infarction, 20 mg/kg per min or even more are sometimes necessary to induce the improvement in myocardial contractility. In the presence of a significant stenosis in the infarct-related vessel, a biphasic response may be observed: an initial improvement in wall thickening during low-dose dobutamine is followed by a worsening of contractility at higher doses when the ischemic threshold is reached. Beta blockers should be stopped at least 24 –36 hours before the test. In patients with severe coronary artery stenosis who present tachycardia at baseline, the ischemic threshold may be attained before the administration of the inotropic agent.
FURTHER PERSPECTIVES Echocardiography provides the opportunity to noninvasively explore hemodynamic variables during pharmacologic or exercise stress test. It could also be useful in heart failure associated with valvular disease. The management of patients with critical aortic stenosis and severe left ventricular dysfunction is sometimes extremely difficult. The selection of patients who may benefit from valve replacement can be improved by the measurement of transvalvular gradients and cardiac output during dobutamine administration. The incidence of dynamic mitral regurgitation is underestimated in patients with coronary artery disease. Dynamic mitral regurgitation is ideally evaluated by an exercise stress test, alone or in combination with right heart catheterization. Further studies are needed in this field. Contrast echocardiography has also been found to be a valuable method for detecting myocardial viability. Some investigators suggest that this technique is as accurate as dobutamine echocardiography.23 This technique also provides important information on the presence of microvascular integrity.
CONCLUSIONS Pharmacologic stress echocardiography is a safe and accurate tool for the assessment of contractile reserve. In experienced hands, this method provides clinically relevant information about patients with severe left ventricular dysfunction. Several studies have demonstrated its value in predicting improvement of left ventricular function in patients undergoing revascularization. Other applications need to be studied such as the assessement of valvular dysfunction or hemodynamic parameters during an exercise protocol. 1. Nesto RW, Cohn LH, Wynne J, Holman L, Cohn PF. Inotropic contractile reserve: a useful predictor of increased 5 year survival and improved postoperative left ventricular function in patients with coronary artery disease and reduced ejection fraction. Am J Cardiol 1982;50:39 – 44. 2. Schelbert HR. Merits and limitations of radionuclide approaches to viability and future developments. J Nucl Cardiol 1994;1:86 – 89. 3. Marwick T, MacIntyre W, Lafont A, Nemec J, Salcedo E. Metabolic responses of hibernating and infarcted myocardium to revascularization: a follow-up study of regional perfusion, function and metabolism. Circulation 1992;8:1347–1353. 4. Pie´rard LA, De Landsheere C, Berthe C, Rigo P, Kulbertus H. Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction treated by thrombolysis: a comparison with positron emission tomography. J Am Coll Cardiol 1990;15:1921–1031. 5. Schutz R, Heusch G. Characterization of hibernating and stunned myocardium. Eur Heart J 1995;16(suppl J):19 –25. 6. Rahimtoola SH. The hibernating myocardium. Am Heart J 1989;117:211–213. 7. Flameng W, Suy R, Schwarz F,Borgers M, Piessens J, Thone F, Van Ermen H, De Geest H. Ultrastructural correlates of left ventricular contraction abnormalities in patients with chronic ischemic heart disease: determinants of reversible segmental asynergy post-revascularization surgery. Am Heart J 1981;102:846 – 857. 8. Cigarroa CG, De Filippi CR, Brickner ME, Alvarez LG, Wait MA, Grayburn PA. Dobutamine stress echocardiography identifies hibernating myocardium and predicts recovery of left ventricular function after coronary revascularization. Circulation 1993;88:430 – 436. 9. Afridi I, Keiman NS, Raizner AE, Zoghbi WA. Dobutamine echocardiography in myocardial hibernation: optimal dose and accuracy in predicting recovery of ventricular function after coronary angioplasty. Circulation 1995;91:663– 670. 10. La Canna G, Alfieri O, Giubbibi R, Gargano M, Ferrari R, Visioli O. Echocardiography during infusion of dobutamine for identification of reversible dysfunction in patients with chronic coronary artery disease. J Am Coll Cardiol 1994;23:617– 626. 11. Perrone-Filardi P, Pace L, Prastaro M, Piscione F, Betocchi S, Squame F, Vezzuto P, Soricelli A, Indolfi C, Salvatore M, Chiariello M. Dobutamine echocardiography predicts improvement of hypoperfused dysfunctional myocar-
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dium after revascularization in patients with coronary artery disease. Circulation 1995;91:2556 –2565. 12. Meluzin J, Cigarroa CG, Brickner ME, Cerny J, Spinarova L, Frelich M, Stetka F, Groch L, Grayburn PA. Dobutamine echocardiography in predicting improvement in global left ventricular systolic function after coronary bypass or angioplasty in patients with healed myocardial infarcts. Am J Cardiol 1995;76: 877– 880. 13. Elhendy A, Cornel JH, Roelandt JRTC, van Domburg RT, Fioretti PM. Akinesis becoming dyskinesis during dobutamine stress echocardiography: a predictor of poor functional recovery after surgical revascularization. Chest 1996;110:155–158. 14. Picano E, Marzullo P, Gigli G, Reisenhofer B, Parodi O, Distante A, L’Abbate A. Identification of viable myocardium by dipyridamole-induced improvement in regional left ventricular function assessed by echocardiography in myocardial infarction and comparison with thallium scintigraphy at rest. Am J Cardiol 1992;70:703–710. 15. Picano E, Ostojic M, Varga A, Sicari R, Djordjevic-Dikic A, Nedelikovic I, Torres M. Combined low dose dipyridamole-dobutamine stress echocardiography to identify myocardial viability. J Am Coll Cardiol 1996;27:1422–1428. 16. Williams MJ, Odabashian J, Lauer MS, Thomas JD, Marwick TH. Prognostic value of dobutamine echocardiography in patients with left ventricular dysfunction. J Am Coll Cardiol 1996;27:132–139. 17. Marzullo P, Parodi O, Reisenhofer B, Sambuceti G, Picano E, Distante A, Gimelli A, L’Abbate A. Value of rest thallium-201/technetium-99m sestamibi scans and dobutamine echocardiography for detecting myocardial viability. Am J Cardiol 1993;71:166 –172. 18. Charney R, Schwinger ME, Chun J, Cohen MV, Nanna M, Menegus MA,
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Wexler J, Spindola Franco H, Greenberg MA. Dobutamine echocardiography and resting-redistribution thallium-201 scintigraphy predicts recovery of hibernating myocardium after coronary revascularization. Am Heart J 1994;128:864 – 869. 19. Arnese M, Cornel JH, Salustri A, Maat APWM, Elhendy A, Reijs AEM, Ten Cate FJ, Keane D, Balk AHMM, Roelandt JRTC, Fioretti PM. Prediction of improvement of regional left ventricular function after surgical revascularization: a comparison of low-dose dobutamine echocardiography with 201Tl singlephoton emission computed tomography. Circulation 1995;91:2748 –2752. 20. Vanoverschelde JLJ, D’Hondt AM, Marwick T, Gerber BL, De Kock M, Dion R, Wijns W, Melin JA. Head-to-head comparison of exercise-redistributionreinjection thallium single-photon emission computed tomography and low dose dobutamine echocardiography for prediction of reversibility of chronic left ventricular ischemic dysfunction. J Am Coll Cardiol 1996;28:432– 442. 21. Panza J, Disizian V, Laurienzo J, Curiel R, Katsiyiannia P. Relation between thallium uptake and contractile response to dobutamine: implications regarding myocardial viability in patients with chronic coronary artery disease and left ventricular dysfunction. Circulation 1995;91:990 –998. 22. Baer FM, Voth E, Deutsch HJ, Schneider CA, Schicha H, Sechtem U. Assessment of viable myocardium by dobutamine transesophageal echocardiography and comparison with fluorine-18 fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 1994;24:343–353. 23. DeFilippi C, Willett D, Irani W, Eichhorn E, Velasco C, Grayburn P. Comparison of myocardial contrast echocardiography and low-dose dobutamine stress echocardiography in predicting recovery of left ventricular function after coronary revascularization in chronic ischemic heart disease. Circulation 1995; 92:2863–2868.
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